Datroway, 2nd ADC from AstraZeneca-Daiichi collab, wins first FDA nod in breast cancer

Following a world-first approval in Japan, AstraZeneca and Daiichi Sankyo’s second antibody-drug conjugate has crossed the U.S. regulatory finish line.

The FDA has greenlighted the drug, datopotamab deruxtecan, for HR-positive, HER2-negative breast cancer in patients who have tried prior endocrine-based therapy and chemotherapy. The TROP2-directed ADC will be sold under the brand name Datroway.

Friday’s FDA nod comes three weeks after Datroway’s Japanese go-ahead in a similar indication and arrives two weeks ahead of the U.S. agency’s original target decision date. The companies said the drug will be available by prescription in the U.S. in about two weeks.

Datroway is the second ADC under a partnership between AstraZeneca and Daiichi, following the successful rollout of their HER2 ADC Enhertu. AZ obtained rights to the TROP2 agent in 2020 by paying Daiichi $1 billion upfront while committing up to $5 billion tied to potential regulatory and sales milestones.

Like its Japanese counterpart, the FDA based its approval on results from the TROPION-Breast01 trial, which showed that Datroway could reduce the risk of disease progression or death by 37% compared with chemotherapy in patients who had already received one or two lines of prior chemotherapy. Those in the Datroway arm went a median 6.9 months without disease worsening versus 4.9 months for chemotherapy.

Overall survival performance was similar between the two treatment arms, as Datroway takers lived a median 18.6 months, compared with 18.3 months for control.

Datroway’s FDA nod puts it slightly ahead of Gilead Sciences’ first-in-class Trodelvy in HR+/HER2- breast cancer. Trodelvy’s nod in the disease mandates that besides endocrine-based therapy, eligible patients must have been treated by at least two additional systemic therapies—rather than just one for Datroway—in the metastatic setting.

But breast cancer is hardly the largest potential opportunity for Datroway and the TROP2 class it belongs to. Industry watchers are more interested in the large non-small cell lung cancer (NSCLC) market. 

AZ and Daiichi recently pulled their original FDA filing for Datroway in second-line nonsquamous NSCLC after the phase 3 TROPION-Lung01 study showed mixed results. The pair has refiled in pretreated EGFR-mutated NSCLC using a pooled subgroup analysis from TROPION-Lung01 and the phase 2 TROPION-Lung05 trial. The application is under FDA priority review with a target decision date set for July 12.

Again, even though the EGFR niche might give Datroway a way into NSCLC, it’s less important than the broader NSCLC setting. There, the phase 3 AVANZAR trial for Datroway’s investigational combination with AZ’s Imfinzi and chemo could read out first-line NSCLC data this year. 

Following TROPION-Lung01’s confusing results, AZ, with the assistance of artificial intelligence, developed a new biomarker that measures TROP2 expression both on tumor cell surface and in the cytoplasm. The hope is to enrich likely responders to Datroway. The biomarker has been incorporated into AVANZAR, which was also increased in size to gain more power to mount a statistically significant showing.

AZ and Daiichi have a busy year ahead. Besides Datroway, the partners’ Enhertu is awaiting an FDA decision by Feb. 1 to potentially move the star ADC earlier in HER2-low breast cancer treatment sequence and to tumors with even lower expression of HER2. Enhertu could have five registrational trial readouts this year, including DESTINY-Breast09 in first-line HER2-positive breast cancer and DESTINY-Breast05 and DESTINY-Breast11 in early-stage disease.